PURPOSE: Attention deficit hyperactivity disorder (ADHD) has been known as psychiatric disorder in childhood associated with dopamine dysregulation. In present study, we investigated changes in dopamine transporter (DAT) density of the basal ganglias using I-123 N- (3-iodopropen-2-yl) -2-carbomethoxy-3beta- (4-chlorophenyl) tropane [I-123 IPT] SPECT in children with ADHD before and after methylphenidate treatment. MATERIALS AND METHOD: Nine drug-naive children with ADHD and seven normal children were included in the study. We performed brain SPECT two hours after the intravenous administration of I-123 IPT and made both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of specific/nonspecific DAT binding ratios in the basal ganglia. All children with ADHD reperformed [123I]IPT SPECT after treatment with methylphenidate (0.7mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methylphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/nonspecific DAT binding ratio of basal ganglia. RESULTS: Children with ADHD had a significantly greater specific/nonspecific DAT binding ratio of the basal ganglia comparing to normal children (Right: z = 2.057, p = 0.041; Left: z = 2.096, p = 0.032). Under treatment with methylphenidate in all children with ADHD, specific/nonspecific DAT binding ratio of both basal ganglia decreased significantly greater than before treatment with methylphenidate (Right: t = 3.239, p = 0.018; Left: t = 3.133, p = 0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. CONCLUSIONS: These findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.
Administration, Intravenous ; Attention Deficit Disorder with Hyperactivity* ; Basal Ganglia* ; Brain ; Child* ; Dopamine Plasma Membrane Transport Proteins* ; Dopamine* ; Humans ; Methylphenidate ; Neurotransmitter Agents ; Tomography, Emission-Computed, Single-Photon

BACKGROUND: Models of attention deficit hyperactivity disorder(ADHD) that have proposed a hypodopaminergic state resulting in hypofunction of the prefrontal circuitry have assumed a unitary dopamine system, which largely ignores the distinct functional differences between mesocortical dopamine system and nigrostriatal dopamine system. PURPOSE: The author's goal was to develop a pathophysiological model for ADHD with greater explanotory power than dopaminergic hypofunction hypothesis in prefronal circuitry. MATERIALS AND METHODS: Published clinical findings on ADHD were integrated with data from genetic, pharmacological, neuroimaging studies in human and animals. RESULTS: Molecular genetic studies suggest that three genes may increase the susceptibility to ADHD. The three candidate genes associated with ADHD are each involved in dopaminergic function, and this consistent with the neurobiologic studies implicating catecholamines in the etiology of ADHD. Pharmacological data also provide compelling support for dopamine and noradrenergic hypothesis of ADHD. Neuroimaging studies lend substantial support for the hypothesis that right-sided abnormalities of prefrontal-basal ganglia circuit would be found in ADHD. CONCLUSIONS: The present hypothesis takes advantage of the major differences between the two pertinent dopamine systems. Mesocortical dopamine system, which largely lacks inhibitory autoreceptors, is ideally positioned to regulate cortical inputs, thus improving the signal-to-noise ratio for biologically valued signals. In this circuit, therapeutic doses of stimulants are hypothesized to increase postsynaptic dopamine effects and enhance executive functions. By contrast, symptoms of hyperactivity/impulsivity in ADHD are hypothesized to be associated with relative overactivity of nigrostriatal circuit. This nigrostriatal circuit is tightly regulated by inhibitory autoreceptoors as well as by long distance feedback from the cortex, and slow diffusion of therapeutic doses of stimulant via oral administration is hypothesized to produce a net inhibition of dopaminergic neurotransmission and improves hyperactivity.
Administration, Oral ; Animals ; Attention Deficit Disorder with Hyperactivity* ; Autoreceptors ; Catecholamines ; Diffusion ; Dopamine ; Dopamine Agents ; Executive Function ; Ganglia ; Humans ; Molecular Biology ; Neuroimaging ; Signal-To-Noise Ratio ; Synaptic Transmission

OBJECTIVES: ADHD has been known as psychiatric disorder in childhood associated with dopamine dysregulation. The symptoms of ADHD can be treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). In present study, we investigated DAT density using I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([123I]IPT SPECT) in children with ADHD before and after treatment with methylphenidate. METHODS: Seven drug-naive children with ADHD and eight normal children were included in the study and performed SPECT 2 hours after an intravenous administration of [123I]IPT. All children with ADHD reperformed [123I]IPT SPECT after treatment with methylphenidate (0.7 mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/ nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methylphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/ nonspecific DAT binding ratio of basal ganglia. RESULTS: Children with ADHD had a significantly greater increase of specific/nonspecific DAT binding ratio of right basal ganglia than normal children (Right:z=2.085, p=0.037;Left:z=1.506, p=0.132). Under treatment with methylphenidate in all children with ADHD, specific/nonspecific DAT binding ratio of both basal ganglia decreased significantly greater than before treatment with methylphenidate (Right:t=3.239, p=0.018;Left:t=3.133, p=0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. CONCLUSIONS: The data of this study using methylphenidate in children with ADHD support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.
Administration, Intravenous ; Attention Deficit Disorder with Hyperactivity* ; Basal Ganglia* ; Child* ; Dopamine Plasma Membrane Transport Proteins* ; Dopamine* ; Humans ; Methylphenidate* ; Neurotransmitter Agents ; Tomography, Emission-Computed, Single-Photon*

OBJECTIVE: ADHD has been known as a psychiatric disorder in childhood associated with dopamine dysregulation. In the present study, we investigated dopamine transporter (DAT) density using I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane (I-123-IPT)-SPECT in children with ADHD on the hypothesis that alterations of DAT density in the basal ganglia were suggestive of dopaminergic dysfunction in children with ADHD. METHODS: Nine drug-naive children with ADHD and six normal children were included in the study. We performed brain SPECT two hours after the intravenous administration of I-123-IPT and made both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of specific/nonspecific DAT binding ratios in the basal ganglia. We then investigated the correlation between ADHD Rating Scale (ARS) scores of children with ADHD and specific/nonspecific DAT binding ratios in the basal ganglia. RESULTS: Children with ADHD had significantly greater specific/nonspecific DAT binding ratio of the basal ganglia comparing to normal children. However, no significant correlation were found between ARS scores of children with ADHD and specific/nonspecific DAT binding ratio of basal ganglia in children with ADHD. CONCLUSION: These findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.
Administration, Intravenous ; Attention Deficit Disorder with Hyperactivity* ; Basal Ganglia* ; Brain ; Child* ; Dopamine Plasma Membrane Transport Proteins* ; Dopamine* ; Humans ; Neurotransmitter Agents ; Tomography, Emission-Computed, Single-Photon*

OBJECTIVETo investigate the effects of dopamine and norepinephrine on the renal function in the patients with septic shock.

METHODSEighty-seven patients with septic shock were divided into three groups (group A, B, C) according to the biggest infusing rate of norepinephrine, with the infusing rate of 0.5 - 0.9, 1.0 - 1.5, 1.6 - 2.0 microg x kg(-1) x min(-1), respectively. Mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB) and urine beta(2)-microglobulin (Ubeta(2)-MG) as well as APACHE III score in all the patients were detected.

RESULTSBefore anti-shock therapy was given, hypotension, tachycardia and oliguria occurred in all the 87 patients, and CRE, BUN, U-ALB, Ubeta(2)-MG and APACHE III score were abnormal in most cases. With the anti-shock therapy, MAP, HR, urine output and BUN, CRE in all patients returned to normal levels gradually, and U-ALB, Ubeta(2)-MG levels and APACHE III score also restored but still remained abnormal.

CONCLUSIONSThe first aim of treating septic shock should be restoring the organ blood supply, and based on volume resuscitation, dopamine, noradrenaline and other vasoactive drugs could be combined to maintain circulatory stability.

APACHE ; Adult ; Aged ; Blood Transfusion ; Cardiotonic Agents ; administration & dosage ; Combined Modality Therapy ; Dopamine ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Kidney ; drug effects ; physiopathology ; Male ; Middle Aged ; Norepinephrine ; administration & dosage ; Retrospective Studies ; Shock, Septic ; physiopathology ; therapy ; Vasoconstrictor Agents ; administration & dosage

OBJECTIVETo investigate the protective effects of small dose of dopamine on the intestinal mucosa of scalded rats in shock stage.

METHODSWistar rats inflicted by 30% TBSA of III degree scalding were employed as the model. The rats were pre-placed with cardiac catheter before and were resuscitated intravenously after injury. The scalded rats were treated by routine (control) and small dose of dopamine (3 micro g.kg(-1).min(-1)), respectively. The changes of rat serum levels of diamine oxidase (DAO), malondialdehyde (MDA) and lactic acid (LA) were observed after treatment. And the pathomorphological changes of the intestine were scored.

RESULTSThe general condition of the rats with dopamine treatment in shock stage was better than that in control group. The rat serum levels of MDA, LA and DAO decreased obviously, especially during 3 to 12 postburn hours (PBHs) after treatment by small dose of dopamine. The pathomorphological scoring of ileum in dopamine treating group was better than that in control.

CONCLUSIONThe intestinal mucosa of severely scalded rats in shock stage could be well protected by small dose of dopamine.

Animals ; Burns ; pathology ; Disease Models, Animal ; Dopamine ; administration & dosage ; pharmacology ; Intestinal Mucosa ; drug effects ; physiology ; Male ; Protective Agents ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar

The purpose of this study is to investigate whether the combination of green tea extract (GTE) and L-theanine has an anxiolytic effect by oral administration through behavioral tests and neurtransmitters (or hormone) anaylses. Four week oral administration of GTE (24 mg/kg), L-theanine (4 mg/kg) or their combination showed anxiety-reducing effects determined by increasing numbers of head-dips in a hole board test and reducing retention time in a rota-rod test without changing spontaneous locomotor activity. Biochemical analyses indicated that the test materials decreased dopamine (DA), noradrenaline (NA), corticosterone (CS) and increased serotonin (5-HT) levels in brain cortex, hippocampus, and striatum, which suggests a possible mechanism of previous behavioral tests. Although the synergistic effects of GTE and L-theanine combination were not observed on the behavioral test, its effects on neurotransmitters (NA, CS) were synergistic and comparable to diazepam (2 mg/kg i.p.) with much less muscle relaxation side effect. Therefore, a combination of GTE and L-theanine may be useful as a functional food ingredient having an anxiolytic effect.
Administration, Oral ; Anti-Anxiety Agents ; Brain ; Corticosterone ; Diazepam ; Dopamine ; Functional Food ; Hippocampus ; Motor Activity ; Muscle Relaxation ; Neurotransmitter Agents ; Norepinephrine ; Retention (Psychology) ; Serotonin ; Tea

PURPOSE: Levodopa is the most effective anti-Parkinsonian agent. It has also been known to exhibit analgesic properties in laboratory and clinical settings. However, studies evaluating its effects on neuropathic pain are limited. The aim of the present study was to examine the anti-allodynic effects of levodopa in neuropathic rats. MATERIALS AND METHODS: Sprague-Dawley male rats underwent the surgical procedure for L5 and L6 spinal nerves ligation. Sixty neuropathic rats were randomly divided into 6 groups for the oral administration of distilled water and levodopa at 10, 30, 50, 70, and 100 mg/kg, respectively. We co-administered carbidopa with levodopa to prevent peripheral synthesis of dopamine from levodopa, and observed tactile, cold, and heat allodynia pre-administration, and at 15, 30, 60, 90, 120, 150, 180, and 240 min after drug administration. We also measured locomotor function of neuropathic rats using rotarod test to examine whether levodopa caused side effects or not. RESULTS: Distilled water group didn't show any difference in all allodynia. For the levodopa groups (10-100 mg/kg), tactile and heat withdrawal thresholds were increased, and cold withdrawal frequency was decreased dose-dependently (p<0.01). In addition, levodopa induced biphasic analgesia. Different dosage of levodopa did not impact on the rotarod time (p>0.05). CONCLUSION: Levodopa reversed tactile, cold and heat allodynia in neuropathic rat without any side effects.
Animals ; Carbidopa/administration & dosage/adverse effects/therapeutic use ; Dopamine Agents/administration & dosage/adverse effects/*therapeutic use ; Hyperalgesia/*drug therapy ; Levodopa/administration & dosage/adverse effects/*therapeutic use ; Male ; Neuralgia/*drug therapy ; Rats ; Rats, Sprague-Dawley ; Rotarod Performance Test

Stress and emotion are associated with several illnesses from headaches to heart diseases and immune deficiencies to central nervous system. Terminalia arjuna has been referred as traditional Indian medicine for several ailments. The present study aimed to elucidate the effect of T. arjuna bark extract (TA) against picrotoxin-induced anxiety. Forty two male Balb/c mice were randomly divided into six experimental groups (n = 7): control, diazepam (1.5 mg·kg), picrotoxin (1 mg·kg) and three TA treatemt groups (25, 50, and 100 mg/kg). Behavioral paradigms and PCR studies were performed to determine the effect of TA against picrotoxin-induced anxiety. The results showed that TA supplementation increased locomotion towards open arm (EPM) and illuminated area (light-dark box test), and increased rearing frequency (open field test) in a dose dependent manner, compared to picrotoxin (P < 0.05). Furthermore, TA increased number of licks and shocks in Vogel's conflict. PCR studies showed an up-regulation of several genes, such as BDNF, IP, DL, CREB, GABA, SOD, GPx, and GR in TA administered groups. In conclusion, alcoholic extract of TA bark showed protective activity against picrotoxin in mice by modulation of genes related to synaptic plasticity, neurotransmitters, and antioxidant enzymes.
Animals ; Antioxidants ; metabolism ; Anxiety Disorders ; drug therapy ; genetics ; metabolism ; psychology ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; Dopamine Agents ; administration & dosage ; GABA Agents ; administration & dosage ; Glutathione Peroxidase ; genetics ; metabolism ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Neuronal Plasticity ; drug effects ; Neurotransmitter Agents ; metabolism ; Phytotherapy ; Picrotoxin ; adverse effects ; Plant Bark ; chemistry ; Plant Extracts ; administration & dosage ; Serotonin Agents ; administration & dosage ; Superoxide Dismutase-1 ; genetics ; metabolism ; Terminalia ; chemistry

OBJECTIVETo investigate the neuroprotective effects and mechanisms of Chunxiong Chatiao pulvis (CXCT) on the MPTP-induced dopaminergic neurodegneration in mice model of PD.

METHODThree to five months old male mice were randomly divided into following six treatment groups (NS + NS, 50 mg x kg(-1) CXCT + NS, 25 mg x kg(-1) CXCT + MPTP, 50 mg x kg(-1) CXCT + MPTP, 75 mg x kg(-1) CXCT + MPTP, NS + MPTP) (n = 8/group). For behavioral measurement, the mice were evaluated for their motor coordination by pole-test; Striatal dopamine content of mice was measured using standard reverse-phase HPLC; Number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra of mice was detected by immunohistochemistry; SOD activity in the substantia nigra of mice were measured by fluorimetry.

RESULTThe score of pole test (25, 50, 75 mg x kg(-1)), the striatal dopamine contents (75 mg x kg-1), the residual DA contents (75 mg x kg(-1)) and the SOD activity in substantia nigra (50, 75 mg x kg(-1)) all showed that, the CXCT-pretreated groups significantly higher than that of the group NS + MPTP (P < 0.05 or P < 0.01).

CONCLUSIONChuanxiong Chatiao pulvis improved the motor deficit in MPTP-induced mice, and attenuate MPTP-induced dopaminergic neurodegeneration in mice. Importantly, the neuroprotective effect of Chuanxiong Chatiao pulvis against dopaminergic neurodegeneration may be associated with its strong antioxidant capacity in vivo.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; adverse effects ; Animals ; Disease Models, Animal ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity ; drug effects ; Neuroprotective Agents ; administration & dosage ; Parkinson Disease ; drug therapy ; metabolism ; physiopathology ; Random Allocation